Individual data of 99 patients treated with SG in the Institut Curie Hospitals between May 2021 and January 2023 are reported. Data were collected until January 20th, 2023. Baseline demographic and clinicopathological characteristics of patients are shown in Table 1. All patients were women, with a median age of 55 years, 12% had de novo metastatic disease, and 31% had brain metastases. On genetic data, 8% had known BRCA1/BRCA2 mutation: 7 patients had germline mutation and only one had somatic mutation with no associated germline mutation. Patients had previously received a median of two lines [1,2,3,4,5,6,7,8,9,10] of treatment in advanced setting, 28% and 6% had previously received anti-PD-1/PD-L1 and PARP inhibitors, respectively. All patients had mTNBC, of whom 26% had non-triple-negative primary breast cancer (estrogen receptor and/or progesterone receptor ≥ 10%) with proven triple-negative metastatic relapse. In this cohort, 48% of the patients met the inclusion criteria for the main published analysis of the ASCENT study.

After a median follow-up of 9.7 months, median PFS was 3.9 months (95%CI[3.4–5.0]) and median OS was 8.6 months (95%CI[7.1–11.9]) (Fig. 1). The ORR was 29% (95%CI[21%–39%]): N = 2/99 patients (2%) had a complete response (CR) as best response, N = 27/99 (27%) had a partial response (PR), N = 23/99 (23%) had a stable disease (SD), N = 44/99 (44%) had a progressive disease (PD), and N = 3/99 (3%) had a non-evaluable disease. Among patients who met the eligibility criteria for ASCENT study publication (N = 48), median PFS was 4.4 months (95%CI[3.5–7.0]) and median OS was 10.6 months (95%CI[9.3–NR]) (Appendix 1).

Progression-free survival and overall survival

Among patients with brain metastases, median PFS was 3.7 months (95%CI[2.6–6.2]) and median OS was 6.7 months (95%CI[6.3–NR]) (Fig. 2). While 11 patients had stable and previously treated brain metastases, 20 had progressive central nervous system metastatic disease before SG administration, of which 11 (55%) were treated with SG alone, 4 (20%) with SG and whole brain radiation therapy (WBRT), 3 (15%) with SG and stereotactic radiation therapy (SRT) and 2 (10%) with SG and intrathecal chemotherapy for leptomeningeal metastases (methotrexate) (Fig. 3). Six patients treated with SG alone had radiologically evaluable cerebral disease according to RECIST 1.1, 50% (N = 3/6) had a partial intracranial response. The best intracranial response is shown in Fig. 4. We could not report intracranial PFS due to an inconsistent and heterogeneous monitoring. Among the 6 patients treated with SG and local treatment with evaluable cerebral disease, N = 2/3 patients had intracranial partial response with SG + WBRT (one could not be evaluated) and N = 2/3 patients had intracranial partial response with SG + SRT. We cannot report an ORR for the two patients treated with concomitant SG and intrathecal methotrexate for leptomeningeal disease, but the first patient had clinical progression leading to death after one cycle, and the second achieved a complete cytological and biochemical response assessed on cerebrospinal fluid, resulting in the control of the leptomeningeal disease for 4 months.

Progression-free survival and overall survival according to brain metastases

Patients with central nervous system metastases (N = 31): description and pattern of response to SG

Best intracranial response with sacituzumab govitecan alone (without radiotherapy). Magnetic resonance imaging (MRI), T1 sequence with gadolinium injection. 1A/1B: target brain metastases before SG; 2A/2B: target brain metastases after 4 months with SG alone, without any radiation therapy

Of the 99 treated patients, 75 (76%) discontinued SG due to progressive disease (N = 70; 93%), toxicity (N = 1; 1%), physical deterioration (N = 3; 4%), or the patient’s request (N = 1; 1%). Twenty-four patients were on treatment at data cut-off. The median duration of treatment was 3.4 months, corresponding to 5 cycles of SG. Of the 75 patients who discontinued SG, 25% (N = 19) received exclusive palliative care and 75% (N = 56) received further anti-tumor treatment: the next line was mainly standard chemotherapy (N = 48), some patients were included in a clinical trial (N = 6) or received PARP inhibitor (N = 1) or another ADC (N = 1) (Appendix 2).

Univariate and multivariate analyses were undertaken to explore the factors associated with PFS and OS (Table 2). We reported no subgroup with significant better PFS. An altered PS (≥ 2) and liver metastases were associated with lower OS in univariate analysis (HR 2.0, 95%CI[1.0–3.8] and HR 1.8, 95%CI[1.1–3.3], respectively), confirmed in multivariate analysis (HR 2.2, 95%CI[1.2–4.3] and HR 2.0, 95%CI[1.1–3.6], respectively) (Fig. 5).

Overall survival according to performance status and liver metastases

Out of 99 treated patients, one experienced toxicity leading to SG discontinuation (grade 4 neutropenia). Dose reductions were required in 17 patients (17%) within a median of 3 cycles [2,3,4,5,6,7,8,9,2,3,4,5,6,7,8,9,10,11]. The main limiting toxicity was hematological (N = 9) including neutropenia (N = 6), febrile neutropenia (N = 2), and anemia (N = 1). Limiting gastrointestinal toxicity was also common (N = 6) with diarrhea grade 2 (N = 1) or 3 (N = 5) which could be associated with radiological colitis (N = 2). Other toxicities were liver enzyme elevation (N = 1) and physical deterioration (N = 1). There was no related death to SG.